Marek Lalli

Feasibility of achieving the 2025 WHO global tuberculosis targets in South Africa, China, and India: a combined analysis of 11 mathematical models.

Summary Background The post-2015 End TB Strategy proposes targets of 50% reduction in tuberculosis incidence and 75% reduction in mortality from tuberculosis by 2025. We aimed to assess whether these targets are feasible in three high-burden countries with contrasting epidemiology and previous programmatic achievements. Methods 11 independently developed mathematical models of tuberculosis transmission projected the epidemiological impact of currently available tuberculosis interventions for prevention, diagnosis, and treatment in China, India, and South Africa. Models were calibrated with data on tuberculosis incidence and mortality in 2012. Representatives from national tuberculosis programmes and the advocacy community provided distinct country-specific intervention scenarios, which included screening for symptoms, active case finding, and preventive therapy. Findings Aggressive scale-up of any single intervention scenario could not achieve the post-2015 End TB Strategy targets in any country. However, the models projected that, in the South Africa national tuberculosis programme scenario, a combination of continuous isoniazid preventive therapy for individuals on antiretroviral therapy, expanded facility-based screening for symptoms of tuberculosis at health centres, and improved tuberculosis care could achieve a 55% reduction in incidence (range 31–62%) and a 72% reduction in mortality (range 64–82%) compared with 2015 levels. For India, and particularly for China, full scale-up of all interventions in tuberculosis-programme performance fell short of the 2025 targets, despite preventing a cumulative 3·4 million cases. The advocacy scenarios illustrated the high impact of detecting and treating latent tuberculosis. Interpretation Major reductions in tuberculosis burden seem possible with current interventions. However, additional interventions, adapted to country-specific tuberculosis epidemiology and health systems, are needed to reach the post-2015 End TB Strategy targets at country level. Funding Bill and Melinda Gates Foundation

TIME Impact – a new user-friendly tuberculosis (TB) model to inform TB policy decisions

Tuberculosis (TB) is the leading cause of death from infectious disease worldwide, predominantly affecting low- and middle-income countries (LMICs), where resources are limited. As such, countries need to be able to choose the most efficient interventions for their respective setting. Mathematical models can be valuable tools to inform rational policy decisions and improve resource allocation, but are often unavailable or inaccessible for LMICs, particularly in TB. We developed TIME Impact, a user-friendly TB model that enables local capacity building and strengthens country-specific policy discussions to inform support funding applications at the (sub-)national level (e.g. Ministry of Finance) or to international donors (e.g. the Global Fund to Fight AIDS, Tuberculosis and Malaria).TIME Impact is an epidemiological transmission model nested in TIME, a set of TB modelling tools available for free download within the widely-used Spectrum software. The TIME Impact model reflects key aspects of the natural history of TB, with additional structure for HIV/ART, drug resistance, treatment history and age. TIME Impact enables national TB programmes (NTPs) and other TB policymakers to better understand their own TB epidemic, plan their response, apply for funding and evaluate the implementation of the response.The explicit aim of TIME Impact’s user-friendly interface is to enable training of local and international TB experts towards independent use. During application of TIME Impact, close involvement of the NTPs and other local partners also builds critical understanding of the modelling methods, assumptions and limitations inherent to modelling. This is essential to generate broad country-level ownership of the modelling data inputs and results. In turn, it stimulates discussions and a review of the current evidence and assumptions, strengthening the decision-making process in general.TIME Impact has been effectively applied in a variety of settings. In South Africa, it informed the first South African HIV and TB Investment Cases and successfully leveraged additional resources from the National Treasury at a time of austerity. In Ghana, a long-term TIME model-centred interaction with the NTP provided new insights into the local epidemiology and guided resource allocation decisions to improve impact.

Cost-effectiveness and resource implications of aggressive action on tuberculosis in China, India, and South Africa: a combined analysis of nine models.

BACKGROUND The post-2015 End TB Strategy sets global targets of reducing tuberculosis incidence by 50% and mortality by 75% by 2025. We aimed to assess resource requirements and cost-effectiveness of strategies to achieve these targets in China, India, and South Africa. METHODS We examined intervention scenarios developed in consultation with country stakeholders, which scaled up existing interventions to high but feasible coverage by 2025. Nine independent modelling groups collaborated to estimate policy outcomes, and we estimated the cost of each scenario by synthesising service use estimates, empirical cost data, and expert opinion on implementation strategies. We estimated health effects (ie, disability-adjusted life-years averted) and resource implications for 2016-35, including patient-incurred costs. To assess resource requirements and cost-effectiveness, we compared scenarios with a base case representing continued current practice. FINDINGS Incremental tuberculosis service costs differed by scenario and country, and in some cases they more than doubled existing funding needs. In general, expansion of tuberculosis services substantially reduced patient-incurred costs and, in India and China, produced net cost savings for most interventions under a societal perspective. In all three countries, expansion of access to care produced substantial health gains. Compared with current practice and conventional cost-effectiveness thresholds, most intervention approaches seemed highly cost-effective. INTERPRETATION Expansion of tuberculosis services seems cost-effective for high-burden countries and could generate substantial health and economic benefits for patients, although substantial new funding would be required. Further work to determine the optimal intervention mix for each country is necessary. FUNDING Bill & Melinda Gates Foundation.

Can tuberculosis patients in resource-constrained settings afford chest radiography?

Even when tuberculosis (TB) care is free, impoverished patients and their households continue to incur unmanageable costs due to seeking and staying in care for the full duration of anti-TB treatment [1]. By aggravating household vulnerability, these costs can prevent or delay diagnosis, treatment and successful outcome, leading to increased TB transmission, morbidity and mortality [2–4]. The new World Health Organization (WHO)s End TB Strategy places greater emphasis on ensuring universal free access to care, and it includes a target of elimination of associated catastrophic costs for TB patients and their households by 2020 [5]. In many low- and middle-income countries chest radiographs are not free of charge for TB patients http://ow.ly/SA7l305Yzk2

Catastrophic costs potentially averted by tuberculosis control in India and South Africa: a modelling study

Summary Background The economic burden on households affected by tuberculosis through costs to patients can be catastrophic. WHOs End TB Strategy recognises and aims to eliminate these potentially devastating economic effects. We assessed whether aggressive expansion of tuberculosis services might reduce catastrophic costs. Methods We estimated the reduction in tuberculosis-related catastrophic costs with an aggressive expansion of tuberculosis services in India and South Africa from 2016 to 2035, in line with the End TB Strategy. Using modelled incidence and mortality for tuberculosis and patient-incurred cost estimates, we investigated three intervention scenarios: improved treatment of drug-sensitive tuberculosis; improved treatment of multidrug-resistant tuberculosis; and expansion of access to tuberculosis care through intensified case finding (South Africa only). We defined tuberculosis-related catastrophic costs as the sum of direct medical, direct non-medical, and indirect costs to patients exceeding 20% of total annual household income. Intervention effects were quantified as changes in the number of households incurring catastrophic costs and were assessed by quintiles of household income. Findings In India and South Africa, improvements in treatment for drug-sensitive and multidrug-resistant tuberculosis could reduce the number of households incurring tuberculosis-related catastrophic costs by 6–19%. The benefits would be greatest for the poorest households. In South Africa, expanded access to care could decrease household tuberculosis-related catastrophic costs by 5–20%, but gains would be seen largely after 5–10 years. Interpretation Aggressive expansion of tuberculosis services in India and South Africa could lessen, although not eliminate, the catastrophic financial burden on affected households. Funding Bill & Melinda Gates Foundation.

Ebola: the hidden toll of tuberculosis.

Infectious disease is still a major cause of death in Western Africa.1 Ebola has taken the headlines recently, but the ‘big three’, human immunodeficiency virus (HIV), malaria and tuberculosis disease (TB), are estimated to have killed many more people in these countries over the same period (~40 000 vs. ~11 300),1 and the Ebola epidemic is very likely to have made things worse. In particular, we wish here to highlight the potential impact on the often hidden TB burden.

Saving Lives at Birth; development of a retrospective theory of change, impact framework and prioritised metrics

BackgroundGrand Challenges for international health and development initiatives have received substantial funding to tackle unsolved problems; however, evidence of their effectiveness in achieving change is lacking. A theory of change may provide a useful tool to track progress towards desired outcomes. The Saving Lives at Birth partnership aims to address inequities in maternal-newborn survival through the provision of strategic investments for the development, testing and transition-to-scale of ground-breaking prevention and treatment approaches with the potential to leapfrog conventional healthcare approaches in low resource settings. We aimed to develop a theory of change and impact framework with prioritised metrics to map the initiative’s contribution towards overall goals, and to measure progress towards improved outcomes around the time of birth.MethodsA theory of change and impact framework was developed retrospectively, drawing on expertise across the partnership and stakeholders. This included a document and literature review, and wide consultation, with feedback from stakeholders at all stages. Possible indicators were reviewed from global maternal-newborn health-related partner initiatives, priority indicator lists, and project indicators from current innovators. These indicators were scored across five domains to prioritise those most relevant and feasible for Saving Lives at Birth. These results informed the identification of the prioritised metrics for the initiative.ResultsThe pathway to scale through Saving Lives at Birth is articulated through a theory of change and impact framework, which also highlight the roles of different actors involved in the programme.A prioritised metrics toolkit, including ten core impact indicators and five additional process indicators, complement the theory of change. The retrospective nature of this development enabled structured reflection of the program mechanics, allowing for inclusion of learning from the first four rounds of the program to inform implementation of subsequent rounds.ConclusionsWhile theories of change are more traditionally developed before program implementation, retrospective development can still be a useful exercise for multi-round programs like Saving Lives at Birth, where outputs from the development can be used to strengthen subsequent rounds. However, identifying a uniform set of prioritised metrics for use across the portfolio proved more challenging. Lessons learnt from this exercise will be relevant to the development of pathways to change across other Grand Challenges and global health platforms.

What if they don't have tuberculosis? The consequences and trade-offs involved in false-positive diagnoses of tuberculosis.

False-positive diagnoses are frequent in tuberculosis and have profound consequences, yet are usually overlooked in policy decision making. We describe pathways and trade-offs involved, and their consequences for individuals, households, and health systems. We then discuss steps to mitigate their impact.